1. Experience and innovation in ethical review. ® An Update and Overview of the US Common Rule Regulations David Borasky, MPH, CIP Copernicus Group IRB CAREB – 30 APRIL 2015

2. Objectives for this session In this session, we will…. Review the current US regulatory framework Key requirements for REBs reviewing research subject to us regs Potential changes to the US regulations and national policy

3. US National Research Act July, 1974 National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974-1978) Public Law 93-348

4. Charge to the National Commission Identify the basic ethical principles which should underlie the conduct of biomedical and behavioral research involving human subjects Develop guidelines to assure that such research is conducted in accordance with those principles National Research Act, 1974 (PL 93-348)

5. Belmont Report (1979) Moral framework for US regulations Three fundamental principles: Respect for persons Beneficence Justice 5

6. US Federal Regulations & Policy 45 CFR 46 - Basic DHHS Policy for Protection of Human Research Subjects - Subpart A January 13, 1981 “The Common Rule” - Federal Policy for the Protection of Human Subjects June 18, 1991 Core regulations adopted by most US Departments / Agencies that support or conduct research 6

7. Dept of Education

8. US Federal Regulations & Policy Additional Protections Included in 45 CFR 46: Subpart B - Additional protections for research involving pregnant women and fetuses Subpart C - Additional protections for research involving prisoners Subpart D - Additional protections for research involving children 8

9. Additional Federal Laws Dept of Education 34 CFR 97 Subpart D 34 CFR 98 34 CFR 99 34 CFR 350.4(c) 34 CFR 356.3(c) Dept of Justice 28 CFR 512 Subpart B Dept of Energy Order 443.1 Order 481.1A 10 CFR Part 850 VA 38 CFR 17.85 Dept of Defense 10 USC 980 DoDD 3216.2 DoDD 6000.8 DoDD 6002.2 AFI 40-402 AFI 40-403 AR 70-25 AR 40-38 SECNAVINST 3900.39B NMRDINST 3900.2 BUMEDINST 6000.12 NSHSBETHINST 6000.41A USUHS Instruction 3201 Dept of Homeland Security Subparts

10. US Food and Drug Administration (FDA) Govern US research involving drugs, devices, biologics 21 CFRF 50 – Informed consent 21 CFR 56 – Requirements for IRBs FDA and Common Rule mostly aligned Studies can be subject to both Common Rule and FDA! 10

11. Key Elements of Regulatory Protections Under Common Rule All human subjects research must have prior REB approval Informed consent unless waived An “Assurance” to uphold ethical and regulatory requirements  FWA Mechanism

12. LOOPHOLES Non-federally-funded research, not involving FDA-regulated items, in an institution not holding a FWA Classified (US government) research

13. FDA DHHS (FWA) Other research covered by FWA Federally Funded 17 Departments & Agencies Subpart A  Common Rule Subpart B Subpart C Subpart D 45 CFR 46 Dan Nelson Applicability of Regulations

14. The Federalwide Assurance Common Rule requires written “assurance of compliance” HHS/OHRP uses FWA mechanism Other departments accept FWA or have similar mechanism FWA is promise to follow applicable U.S. regulations Required of all engaged sites in HHS-funded research

15. REB written procedures OHRP / FDA required written procedures: 1. The procedures which the REB will follow for conducting its initial review of research; Use of primary reviewers Approvals with contingencies 2. The procedures which the REB will follow for conducting its continuing review of research Meaningful, substantive

16. REB written procedures 3. The procedures which the REB will follow for reporting its findings and actions to investigators and the institution which institutional offices / officials are notified of REB findings and actions and how notification to each is accomplished; 4. The procedures which the REB will follow for determining which projects require review more often than annually Level of risk Population being studied Previous PI compliance issues

17. REB written procedures 5. The procedures which the REB will follow for determining which projects need verification from sources other than the investigators that no material changes have occurred since previous REB review Randomly selected projects; Complex projects involving unusual levels or types of risk to subjects Investigators with past compliance issues

18. REB written procedures 6. The procedures which the REB will follow for ensuring prompt reporting to the REB of proposed changes in a research activity, and for ensuring that such changes in approved research, during the period for which REB approval has already been given, may not be initiated without REB review and approval except when necessary to eliminate apparent immediate hazards to the subject Training programs and materials for investigators, Specific directives included in approval letters to investigators Random audits of research records

19. REB written procedures 7. The procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, any Department or Agency head, and OHRP of: ○ Any unanticipated problems involving risks to subjects or others; ○ Any serious or continuing noncompliance with 45 CFR Part 46 or the requirements or determinations of the IRB; and ○ Any suspension or termination of IRB approval.

20. REB written procedures Guidance available at: http://www.hhs.gov/ohrp/policy/irbgd107.html http://www.hhs.gov/ohrp/policy/irbgd107.html Many institutions post their institutional policies online – do not be afraid to borrow!

21. New Era of Change? Common Rule regulations largely unchanged since 1991 Regulations could not anticipate 21 st century research realities Changes proposed on multiple fronts

22. HHS/OHRP - Potential Notice of Proposed Rule Making (NPRM) Advanced NPRM published in 2011 Multiple proposed changes Single IRB All specimens = identifiable Revisions to exempt and expedited Numerous comments from regulated community

23. NPRM Concerns 4 years since ANPRM Lack of transparency Disagreement among Common Rule agencies  end of Common Rule? Further separation from FDA regs?

24. NIH Single REB Policy Would require single REB for all multi-site research studies (US domestic only) Only NIH-funded research Many institutional REBs not equipped to serve as central REB Concerns about REB policy being dictated outside of the regulatory structure

25. Newborn Dried Bloodspot Law New law signed in December 2014 Affects HHS-funded research using residual newborn dried bloodspots Bloodspots = human subject, even when otherwise considered de-identified REB may not waive informed consent for research user

26. 21 st Century Cures Initiative Proposed healthcare legislation Would expand regulatory oversight / eliminate loopholes Not yet clear which current regulations would be expanded, or if replaced with new

27. Other issues related to REBs Big Data Who controls the data Consent issues Research involving social media Facebook Study Return of Results General Individual

28. Questions, Comments and Discussion